Effect of Tysabri in Patients With Relapsing-Remitting Multiple Sclerosis: A Follow-up Magnetization Transfer Imaging (MTI) Study

September 6, 2011 updated by: Robert Zivadinov, MD, PhD, University at Buffalo

Effect of Natalizumab (Tysabri®) on Remyelination in Patients With Relapsing-remitting Multiple Sclerosis. A Follow-up Voxel-wise Magnetization Transfer Imaging Study.

The primary objective of this study is to define the effect of Tysabri in patients with relapsing-remitting (RR) multiple sclerosis (MS) over 2 years. The investigators will also explore the extent of remyelination in MS patients treated with Tysabri over 2 years.

A secondary objective of this study is to investigate differences in the capacity for remyelination between patients who do or do not respond to Tysabri monotherapy during the same 24 months.

A tertiary objective of this study is to monitor Tysabri effect in MS antiphospholipid antibodies positive and MS antiphospholipid antibodies negative patients and to determine perfusion differences according to the antiphospholipid antibodies positivity status.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Magnetization transfer imaging (MTI) is a widely used tool for characterizing the evolution of multiple sclerosis (MS) lesions and normal appearing brain tissue (NABT). As remyelination and demyelination are heterogeneous in each lesion and NABT, techniques such as voxel-wise based MTR dynamic mapping may help predict an individual's clinical course, as well as the effect of treatment, by revealing evidence of myelin repair and neuroprotection.

Natalizumab (Tysabri) showed a robust effect on the decrease of inflammation in phase II and III clinical trials, as evidenced by the decrease in Gd enhancing and T2 lesions and on the decrease of clinical activity as measured by reduction of clinical relapses and progression of disability. The effect of Tysabri on non-conventional measures is only partially known.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
85

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Buffalo, New York, United States, 14203
        • Jacobs Neurological Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

MS patients that are followed at the Jacobs Neurological Institute, University at Buffalo, Buffalo NY.

Description

Inclusion Criteria:

  • Patient diagnosed with clinically definite MS according to the Polman criteria
  • Age 18-65
  • Have a RR disease course
  • Have EDSS scores less than or equal to 5.5 {Kurtzke, 1983 #15}
  • Have disease duration less than 20 years
  • Fulfilled the TOUCH enrollment requirements and started on Tysabri monotherapy
  • Signed informed consent
  • None of the exclusion criteria

Exclusion Criteria:

  • Primary progressive, secondary progressive, or progressive relapsing MS. Primary progressive, secondary progressive or progressive relapsing multiple sclerosis.
  • A clinically significant infectious illness (e.g., cellulitis, abscess, pneumonia, septicemia) within 30 days prior to drug start.
  • History of, or abnormal laboratory results indicative of, any significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric, renal, and/or other major disease that, in the opinion of the investigator, would preclude the administration of natalizumab for the duration of the study.
  • History of severe allergic or anaphylactic reactions or known drug hypersensitivity.
  • Abnormal blood tests, performed at the screening visit, which exceed any of the limits defined below:
  • ALT/ SGPT, or AST/ SGOT > three times the upper limit of normal (i.e., 3xULN).
  • Total white blood cell (WBC) count <2,300/mm3.
  • Platelet count <100,000/mm3.
  • Creatinine > 2xULN.
  • Prothrombin time (PT) > ULN.
  • Any prior treatment during the 2 weeks prior to study screening with agents such as IFN-β, GA, IVIG, or on the following immunosuppressant therapies for less than 3 months: mitoxantrone, cyclophosphamide, cladribine, fludarabine, cyclosporine, azathioprine, methotrexate, Cellcept, etc.
  • History of alcohol or drug abuse within 2 years prior to randomization.
  • Female subjects who are not postmenopausal for at least 1 year, surgically sterile, or willing to practice effective contraception (as defined by the investigator) during the study. The rhythm method is not to be used as the sole method of contraception.
  • Nursing mothers, pregnant women, and women planning to become pregnant while on study.
  • Unwillingness or inability to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that is likely to affect the subject's ability to comply with the study protocol.
  • Any other reasons that, in the opinion of the Investigator, indicate that the subject is unsuitable for enrollment into this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
1
63 patients with relapsing-remitting Multiple Sclerosis who are enrolled in the TOUCH program and have been taking Tysabri monotherapy for 2 years.
Drug: Tysabri

Infusion of TYSABRI® 300 mg in 100 mL 0.9% Sodium Chloride Injection, USP over approximately one hour at month 0 and 12 and 24 months. After the infusion is complete, flush with 0.9% Sodium Chloride Injection, USP.

Use of filtration devices during administration has not been evaluated. Other medications should not be injected into infusion set side ports or mixed with TYSABRI®.

TYSABRI® concentrate is supplied as 300 mg natalizumab in a sterile, single-use vial free of preservatives. Each package contains a single-use vial.

Other Names:
  • Natalizumab
2
22 age- and sex-matched normal controls who completed 1 year follow-up.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
To define the effect of Tysabri monotherapy on a voxel-wise basis using magnetization transfer ratio dynamic mapping of the lesions and normal appearing brain tissue in patients with relapsing-remitting multiple sclerosis.
Time Frame: 2 years
2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
To investigate differences in the capacity for remyelination measured by MTR between patients who do or do not respond to Tysabri monotherapy.
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University at Buffalo

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Biogen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2007

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2009

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2010

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 9, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 10, 2009

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 13, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 7, 2011

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 6, 2011

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BNAC/Tysabri/01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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